Lung remodeling diseases (LRD) are a group of disorders that lead to progressive loss of function in the alveoli. Although the disease typically involves an initial acute inflammatory response, many patients do not seek treatment until the disease has progressed to a more advanced chronic phase. LRD may be due to a number of different underlying factors. Exposure to occupational or environmental inhalants, including inhalation of organic dust, inorganic dust, cigarette smoke or noxious gases can often result in LRD. First line treatment requires identification and removal of the causative agent from the patient's environment. LRD can also be caused by exposure to certain drugs or ionizing radiation, as may occur during chemo- or radiation therapy in cancer patients. LRD may also result from an exaggerated immune response, such as in sarcoidosis, or part of a more systemic collagen vascular disorder. In many cases, the underlying cause of LRD remains unknown.
Although the initiating agent(s) or circumstances may vary, the immunopathogenic response of lung tissues generally involves a similar course of events. The initial response is inflammation of the air spaces and alveolar walls, causing an acute alveolitis. If the condition persists, inflammation spreads to the interstitium and vasculature of the alveoli. At early stages, the alveolar and adjacent capillary endothelial cells become leaky, leading to alveolar and septal edema, and the number of immune cells found in bronchoalveolar lavage (BAL) fluid and/or sputum increases. In particular, the number of polymorphonuclear leukocytes (PMNs), which normally comprise about 1-3% of the cellular component of BAL and/or sputum, can increase to 20% or more. Persistence in the inflammatory response leads to desquamation of the wall of the alveoli and compensatory proliferation of fibroblast in the interstitium. The resultant scarring of lung tissue leads to significant alterations in gas exchange and ventilatory function. LRD can also involve the bronchioles, and patients may present with bronchiolitis.
Current treatment options for LRD are limited and do not provide long-term improvement in most patients. Corticosteroids such as prednisone are often provided to reduce the inflammation associated with LRD. However, immunosuppressant therapy can lead to increased infection in the compromised lung and a worsening of the condition. As the treatment options for patients with lung remodeling disease are inadequate, new methods and medicaments for the treatment of lung remodeling disease are therefore desirable.